The cephalosporin antibiotics stem from the discovery of cephalosporin C produced in the fermentation of Cephalosporium acremonium.
The parent group of antibiotics possess in common the basic structural features represented by the following general formula for a 7-acylamidocephalosporanic acid ##SPC3##
And are characterized by a .beta.-lactam ring fused to a dihydrothiazine ring bearing an acetoxymethyl group in the 3-position; a carbon to carbon double bond in the 3-position and a carboxylic acid function in the 4-position. Cephalosporin C is represented by the above formula when the acyl group is 5-aminoadipoyl.
Numerous modifications have been made in the parent structure, including those in which the acetoxy function at the 3-methyl position has been replaced by another group.
Among the variations which have led to new and useful antibiotics have been the desacetoxycephalosporanic acids represented by the formula ##SPC4##
Wherein the 3-position is substituted by a methyl group in place of the acetoxymethyl group of the cephalosporanic acids.
Heretofore, two general methods have been employed to prepare the desacetoxycephalosporanic acids. In the first of these methods, cephalosporin C is converted to 7-aminocephalosporanic acid (7-ACA) by cleaving the 5-aminoadipoyl side chain therefrom, for example, by the procedure described by Morin et al. in U.S. Pat. No. 3,188,311. The 7-ACA is then subjected to hydrogenolysis according to the method described in J. Med. Chem., 7, 117 (1964) to provide 7-aminodesacetoxycephalosporanic acid (7-ADCA). Acylation of 7-ADCA with the desired acyl moiety according to well known acylation methods thus provides the 7-acylamidodesacetoxycephalosporanic acid.
The catalytic hydrogenolysis of cephalosporin C has been reported to yield desacetoxycephalosporin C, Biochem J., 79, 377 (1961).
Alternatively, the desired desacetoxycephalosporanic acid can be prepared by the rearrangement of an appropriately substituted penicillanate sulfoxide ester according to the procedure described by U.S. Pat. No. 3,275,626, issued Sept. 27, 1966.
Although the preceding methods for the preparation of the desacetoxycephalosporanic acids are valuable synthetic methods, the search for more efficient and economical processes for the preparation of these antibiotics continues.